Variant chr20-23985959-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_178311.3(GGTLC1):c.320C>T(p.Ser107Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,459,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S107P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

GGTLC1
NM_178311.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Variant links:

Genes affected

GGTLC1 (HGNC:16437): (gamma-glutamyltransferase light chain 1) This gene encodes a member of the gamma-glutamyl transpeptidase (GGT) family, which are important in the metabolism of glutathione. The most ubiquitously expressed human GGT gene, GGT1, encodes a single transmembrane polypeptide that is post-translationally processed to form a heavy and a light chain. In contrast, the product of this gene only contains homology to the light chain region, and lacks a transmembrane domain. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2008]

GGTLC1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.949

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGTLC1	NM_178311.3 linkuse as main transcript	c.320C>T	p.Ser107Leu	missense_variant	4/6	ENST00000335694.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GGTLC1	ENST00000335694.4 linkuse as main transcript	c.320C>T	p.Ser107Leu	missense_variant	4/6	1	NM_178311.3	P1
GGTLC1	ENST00000278765.8 linkuse as main transcript	c.320C>T	p.Ser107Leu	missense_variant	4/6	1		P1
GGTLC1	ENST00000286890.8 linkuse as main transcript	c.320C>T	p.Ser107Leu	missense_variant	3/5	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250732

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1459656

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726152

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2023

The c.320C>T (p.S107L) alteration is located in exon 4 (coding exon 3) of the GGTLC1 gene. This alteration results from a C to T substitution at nucleotide position 320, causing the serine (S) at amino acid position 107 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.15

T;T;T

Eigen

Benign

0.0064

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.37

M_CAP

Benign

0.0023

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

4.6

H;H;H

MutationTaster

Benign

0.83

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-5.7

D;D;D

REVEL

Benign

0.25

Sift

Benign

0.046

D;D;D

Sift4G

Uncertain

0.041

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.58

MutPred

0.90

Loss of disorder (P = 0.0127);Loss of disorder (P = 0.0127);Loss of disorder (P = 0.0127);

MVP

0.12

MPC

0.56

ClinPred

0.94

GERP RS

-2.1

Varity_R

0.38

gMVP

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over